CLDN18 (Claudin 18)

P3, N=752, Not yet recruiting, Shanghai Chia Tai Tianqing Pharmaceutical Technology Development Co., Ltd.

Combining biomarker-driven immunotherapy and targeted approaches such as PD-1 blockade in MSI-H or EBV-positive tumors, HER2-directed therapy, and CLDN18.2 inhibition, has demonstrated a paradigm shift in the clinical management. This review highlights a pathologist-centered perspective on molecularly defined subgroups, actionable biomarkers, and evolving therapeutic paradigms in CRC and GEJ carcinoma, advancing precision oncology.

P3, N=524, Not yet recruiting, FutureGen Biopharmaceutical (Beijing) Co., Ltd

Clinical trials of Claudin 18.2-targeted therapies (e.g., Zolbetuximab) further expand personalized treatment options...Despite the abundance of research in this field, this paper prioritizes the analysis and discussion of prospective or high-quality retrospective studies that include explicit efficacy prediction endpoints (such as pCR, TRG, AUC) to ensure the reliability of the evidence presented. This review emphasizes that multi-omics integrated predictive models and the clinical translation of targeted therapies represent critical directions for future research, aiming to optimize the neoadjuvant treatment strategies for locally advanced gastric cancer.

Gross intrahepatic mass formation indicates an intrahepatic contextual profile and provides a useful criterion for subclassifying hCCA. This contextual framework shows that hCCA-M and hCCA-NM represent biologically distinct tumor groups.

This proteogenomic framework defines exposure-informed and microbiome-informed gastric cancer subtypes, providing a molecular schema for patient stratification, prevention and actionable therapeutic vulnerabilities.

Among patients undergoing nivolumab treatment, CPS ≥1 was significantly associated with longer survival outcomes in CLDN18.2-positive patients, and a tendency toward improved Nivo-OS in TROP2-positive patients.

Trastuzumab first established HER2-targeted therapy in gastric cancer, but the failure of trastuzumab emtansine (T-DM1) led to a decade-long stagnation until the advent of trastuzumab deruxtecan (T-DXd), which demonstrated robust clinical activity and defined a new standard of care. While bevacizumab failed to improve survival, the anti-VEGFR2 antibody ramucirumab emerged as an effective second-line therapy. Immune checkpoint inhibitors, including nivolumab and pembrolizumab, have been incorporated into first-line treatment for PD-L1-positive disease based on landmark trials such as CheckMate 649 and KEYNOTE-811. More recently, the CLDN18.2-targeted antibody zolbetuximab has expanded therapeutic options for biomarker-selected patients. Concurrently, a diverse pipeline of immune-based strategies-such as TROP2-directed ADCs, bispecific antibodies, and CAR-T cell therapies-is undergoing active clinical development. Together, advances in biomarker-driven antibody therapeutics are accelerating personalized cancer care and improving clinical outcomes in patients with gastric cancer.

Additionally, it explores the growing role of artificial intelligence in reshaping cancer drug discovery and development frameworks as potential avenues for future research. In conclusion, innovative approaches in oncology, supported by pharmacological research, ongoing clinical trials, molecular biosciences, and artificial intelligence, are poised to significantly transform cancer treatment.

CLDN18.2-high GEA was more prevalent than previously reported in pivotal trials and showed substantial overlap across molecular subtypes. It was associated with a greater benefit from HER2-targeted therapy but a trend toward poorer outcomes with IO, underscoring the need for biomarker-guided therapeutic strategies in GEA.

The CLDN18.2 expression demonstrated an acceptable concordance between biopsy and surgically resected specimens. However, high prevalence of heterogeneous expression and tendency for CLDN18.2 positivity to shift to negativity following chemotherapy existed.

Discontinuation of 5-FU and supportive care consisting of hydration and rasburicase led to rapid clinical improvement. Chemotherapy, which was resumed after a dosage adjustment, achieved tumor shrinkage and resolved the hydronephrosis. To the best of our knowledge, the present study is the first to describe concurrent TLS and 5-FU-induced encephalopathy during the administration of a zolbetuximab-based regimen and highlights the need for proactive prophylaxis against TLS and for controlling nausea in AGC patients with a high tumor burden, baseline renal impairment, and cachexia.